Biology subjects

Reischauer, S.

Publications and source records attributed to Reischauer, S..

5 recordsLinked to original sources

bioRxiv2026

Junb acts downstream of the Il-11/Stat3 signaling axis to limit tissue damage induced fibro-inflammation during regeneration

Inflammation is essential for regeneration yet can also drive fibroinflammatory remodeling; what determines these opposing outcomes remains unclear. Comparative transcriptomic analyses revealed that injured mouse hearts activated a broad inflammatory program, whereas zebrafish hearts mounted a restricted response characterized by selective il11 induction. This divergence extended across tissues and species: the non-regenerative mammalian injuries examined shared an inflammatory signature distinct from regenerative vertebrate contexts. We identified the AP-1 transcription factor Junb as an Il-11-Stat3-dependent regulator that restrains inflammation during fin fold regeneration. Combined loss of junba and junbb amplified a mammalian-like inflammatory program, increased neutrophil recruitment and fibroinflammatory gene expression, and reduced proliferation and regenerative outgrowth. Strikingly, dexamethasone or ibuprofen substantially restored regeneration in Junb deficient zebrafish larvae, demonstrating that hyperinflammation is a major determinant of regenerative failure. Thus, the Il-11-Stat3-Junb axis maintains a regeneration permissive inflammatory state preventing a regenerative response from shifting toward mammalian-like fibroinflammation.

immunology↗

bioRxiv2021

Myostatin is a negative regulator of adult neurogenesis in zebrafish

Intrinsic and extrinsic inhibition of axonal and neuronal regeneration obstruct spinal cord (SC) repair in mammals. In contrast, adult zebrafish achieve functional recovery after SC damage. While studies of innate SC regeneration have focused on axon regrowth as a primary repair mechanism, how local neurogenesis impacts functional recovery is unknown. We uncovered dynamic expression of myostatin b (mstnb) in a niche of dorsal ependymal progenitors after complete SC transection in zebrafish. Genetic loss-of-function in mstnb impaired functional recovery, although glial and axonal bridging across the lesion were unaffected. Using a series of transgenic reporter lines, we quantified the numbers of stem, progenitor, and neuronal cells in the absence of mstnb. We found neural stem cell proliferation was reduced, while newborn neurons were increased in mstnb null tissues, suggesting mstnb is a negative regulator of neurogenesis. Molecularly, neuron differentiation genes were upregulated, while the neural stem cell maintenance gene fgf1b was downregulated in mstnb mutants. Finally, we show that human FGF1 treatment rescued neuronal gene expression in mstnb mutants. These studies uncover unanticipated neurogenic functions for mstnb in adult zebrafish, and establish the importance of local neurogenesis for functional SC repair.

neuroscience↗

bioRxiv2021

Regenerating insulin-producing β-cells ectopically from a mesodermal origin in the absence of endothelial specification

To investigate the role of the vasculature in pancreatic {beta}-cell regeneration, we crossed a zebrafish {beta}-cell ablation model into the avascular npas4l mutant (i.e. cloche). Surprisingly, {beta}-cell regeneration increased markedly in npas4l mutants owing to the ectopic differentiation of {beta}-cells in the mesenchyme, a phenotype not previously reported in any models. The ectopic {beta}-cells expressed endocrine markers of pancreatic {beta}-cells, and also reduced glucose levels in the {beta}-cell ablation model. Through lineage tracing, we determined that the vast majority of these ectopic {beta}-cells derived from the mesodermal lineage. Notably, ectopic {beta}-cells were found in npas4l mutants as well as following knockdown of the endothelial determinant Etv2. Together, these data indicate that in the absence of endothelial specification, mesodermal cells possess a remarkable plasticity enabling them to form {beta}-cells, which are normally endodermal in origin. Understanding the restriction of this differentiation plasticity will help exploit an alternative source for {beta}-cell regeneration.

developmental biology↗

bioRxiv2019

Functional and structural properties of highly responsive somatosensory neurons in mouse barrel cortex

Sparse population activity is a hallmark of supra-granular sensory neurons in neocortex. The mechanisms underlying sparseness are not well understood because a direct link between the neurons activated in vivo and their cellular properties investigated in vitro has been missing. We used two-photon calcium imaging to identify a subset of neurons in layer L2/3 (L2/3) of mouse primary somatosensory cortex that are highly active following principal whisker vibrotactile stimulation. These high responders were then tagged using photoconvertible green fluorescent protein for subsequent targeting in the brain slice using intracellular patch-clamp recordings and biocytin staining. This approach allowed us to investigate the structural and functional properties of high responders that distinguish them from less active control cells. Compared to less responsive L2/3 neurons, high responders displayed increased levels of stimulus-evoked and spontaneous activity, elevated noise and spontaneous pair-wise correlations, and stronger coupling to the population response. Intrinsic excitability was reduced in high responders, while other electrophysiological and morphological parameters were unchanged. Thus, the choice of which neurons participate in stimulus encoding may largely be determined by network connectivity rather than by cellular structure and function.

neuroscience↗

bioRxiv2018

Genome-wide strategies reveal target genes of Npas4l associated with cardiovascular development in zebrafish

The development of a vascular network is essential to nourish tissues and sustain organ function throughout life. Endothelial cells (ECs) are the building blocks of blood vessels, yet our understanding of EC specification remains incomplete. zebrafish cloche/npas4l mutants have been used broadly as an avascular model, but little is known about the molecular mechanisms of action of the Npas4l transcription factor. Here, to identify its direct and indirect target genes, we combined complementary genome-wide approaches including transcriptome analyses and chromatin immunoprecipitation (ChIP). The cross-analysis of these datasets indicates that Npas4l functions as a master regulator by directly inducing a group of transcription factor genes crucial for hematoendothelial specification such as etv2, tal1 and lmo2. We also identified new targets of Npas4l and investigated the function of a subset of them using the CRISPR/Cas9 technology. Phenotypic characterization of tspan18b mutants reveals a novel player in developmental angiogenesis, confirming the reliability of the datasets generated. Collectively, these data represent a useful resource for future studies aimed to better understand EC fate determination and vascular development.

developmental biology↗